Recent studies in our laboratory and others have demonstrated variation in adipose tissue enzyme activities with diet as well as among obese and nonobese groups of human subjects. The proposed research will determine whether diet-induced and obesity-associated variations in these enzyme activities are related to insulin-sensitivity or insulin-resistance in vivo as well as in adipose tissue in vitro. The role of serum factors in these variations will be tested directly. Serum samples for in vitro incubations and adipose tissue (by needle aspiration) will be obtained from obese and nonobese subjects with normal glucose tolerance, from obese chemical diabetics, and from maturity-onset diabetics. Additional tissues will be obtained at elective surgery. The sera will be tested for acute effects on insulin-sensitivity in adipose tissue in vitro, as well as for chronic effects on insulin-sensitivity and enzyme activities in adipose tissue incubated for several days in the presence of the sera. The effects of a given subject's sera on exogenous adipose tissue will be compared with in vivo insulin-sensitivity, as judged by circulating glucose and insulin concentrations during glucose tolerance tests, as well as with enzyme activities and insulin-sensitivity in vitro in the subject's own tissue in the absence of serum. The effects of different sera on basal and catecholamine-stimulated lipolysis will also be measured. A factor, present in impure commercial preparations of thyrotropin, whose chronic effects include decreased activity of phosphofructokinase in adipose tissue, will be purified, characterized, and its possible effects on insulin-sensitivity and lipolysis explored.